IMMUNOSUPPRESSION COMBINED WITH TONSILLECTOMY IS EFFECTIVE IN CAUCASIAN PATIENTS WITH HIGH-RISK PRIMARY IGA-NEPHROPATHY

Introduction:

There is a robust evidence that tonsillectomy (TE) may be effective in Asian patients with IgA-nephropathy (IgAN), while TE is not a recommended treatment in Caucasians. Faced with a paucity of such data, the goal of this comparative study was to evaluate an efficacy of treatment with immunosuppression combined with tonsillectomy (IST+TE) in Caucasian patients with high-risk primary IgAN. Here, we present an interim analysis of this ongoing study.

Methods:

The study enrolled cases of primary IgAN (n=231, age 34±11 years, 52% male) at high risk of progression. The latter defined as i) proteinuria >1 g/day or ii) the probability of starting dialysis within 5 years >11% or iii) at least one of the following histologic alterations: mesangial proliferation, endocapillary hypercellularity, and cellular crescents. Demographic and clinical parameters at the time of renal biopsy, and renal histology data were used. The follow-up period was 26 (10; 61) months. Outcomes were complete remission (CR), overall (complete or partial) remission (OR), and progression as a composite of ESKD or eGFR decrease of >40% from baseline. All patients received immunosuppressive therapy (steroid monotherapy – 73%, steroids with cyclophosphamide, mycophenolic acid, cyclosporine, or azathioprine – 27%). The prospectively followed experimental group received IST combined with TE (IST+TE, n=90) no earlier than 12 months before and no later than 12 months after the start of IST. In most patients, TE was performed before the start of IST (n=44; 61.1%), and the median time between the IST start and TE was -0.9 (-3.7; 1.5) months. The historic control group comprised subjects undergone only immunosuppressive therapy without TE (IST, n=141). Kaplan-Meyer curves and Cox regression models combined with pseudo-randomisation methods (1:1 propensity score matching of comparison groups and inverse probability of treatment weighting) were applied to compare the efficacy of IST+TE with only IST.

Results:

The rates of OR in IST and IST+TE groups were 65,2% and 86,1%, respectively (p=0.002). In the propensity score matched experimental and control groups, Kaplan-Meyer analyses have shown a remarkably shorter time to remission and slower progression rate favouring the IST+TE combined therapy (Figure). In Cox models, the probabilities of developing OR and CR were significantly higher in the tonsillectomy group compared to IST alone. IST+TE was also associated with a decrease in the likelihood of disease progression (Table).

Conclusions:

Contrary to current recommendations, the study results suggested the combination of tonsillectomy and immunosuppression was effective at inducing disease remission and delaying progression in Caucasian patients with high-risk primary IgAN.

I have potential conflict of interest to disclose.
The study is supported by the Russian Foundation for Scientific Research, grant №23-15-00510 “Intestinal metabolome alteration as a factor in the pathogenesis of IgA nephropathy: an explorative study".

I did not use generative AI and AI-assisted technologies in the writing process.